Genomic Analysis of Colistin and Carbapenem Resistant Klebsiella pneumoniae GC29

Microb Pathog. 2024 Dec 10:107220. doi: 10.1016/j.micpath.2024.107220. Online ahead of print.

Abstract

Objectives: This study aims to sequence and analyze a clinical strain of Klebsiella pneumoniae (GC29) focusing on its antibiotic resistance profiles, virulence traits, and evolutionary lineage. The goal is to provide insights into the challenges of combating multi-drug resistant K. pneumoniae and emphasize the necessity for targeted strategies to address this public health threat.

Methods: Antibiotic resistance profiles of GC29 were determined using disc diffusion assays and MICs according to CLSI guidelines. Genomic analysis was performed to detect antimicrobial resistance and virulence-associated genes. The evolutionary lineage and plasmid content were evaluated through comparative genomic analysis with closely related strains.

Results: GC29 exhibited resistance to 33 FDA-approved antibiotics across various classes including colistin and carbapenem, with high MIC values for Amikacin, Ampicillin, Erythromycin, Colistin, Cefotaxime, Cefixime, Tetracycline, and Kanamycin. Genome analysis revealed multiple antimicrobial resistance genes, including those for β-lactams, sulphonamides, trimethoprim, aminoglycosides, tetracyclines, fosfomycin, and chloramphenicol. Four unique virulence genes (allA, sciN, impF, acpXL) were identified. GC29 belonged to sequence type *703b and carried two plasmids, IncHI1B (317,780 bp) and ColKP3 (12,224 bp), both harboring drug-resistance genes. It clustered closely with strain BA4946, indicating genetic relatedness and shared evolutionary history, with implications for horizontal transfer of multi-drug resistance.

Conclusions: The study underscores GC29's significant threat due to its extensive antibiotic resistance and distinctive virulence factors. This highlights the critical need for enhanced surveillance, rigorous infection control, and innovative therapeutic strategies to address MDR K. pneumoniae effectively. The complex resistance mechanisms and virulence of this pathogen emphasize the growing public health challenge.

Keywords: AMR genes; Antibiotic resistance; K. pneumoniae; Phylogenetic relationship; Virulence Genes; Whole Genome Sequencing.